Hydraulic pressure inducing renal tubular epithelial-myofibroblast transdifferentiation in vitro

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Feiyan LI Xisheng XIE Junming FAN Zi LI Jiang WU Rong ZHENG Department of Nephrology West China Hospital of Sichuan University Chengdu China State Key Laboratory of Biotherapy of Human Disease West China Hospital of Sichuan University Chengdu China Institute of Biomedical Engineering West China Center of Medical Sciences Sichuan University Chengdu China [1 ,1 ,1 ,2 ,1 ,3 ,1 ,1 ,610041 ,2 ,610041 ,3 ,610041 ]
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Objective: The effects of hydraulic pressure on renal tubular epithelial-myofibroblast transdifferentiation (TEMT) were investigated. Methods: We applied hydraulic pressure (50 cmH2O) to normal rat kidney tubular epithelial cells (NRK52E) for different durations. Furthermore, different pressure magnitudes were applied to cells. The morphology, cytoskeleton, and expression of myofibroblastic marker protein and transforming growth factor-β1 (TGF-β1) of NRK52E cells were examined. Results: Disorganized actin filaments and formation of curling clusters in actin were seen in the cytoplasm of pressurized cells. We verified that de novo expression of α-smooth muscle actin induced by pressure, which indicated TEMT, was dependent on both the magnitude and duration of pressure. TGF-β1 expression was significantly upregulated under certain conditions, which implies that the induction of TEMT by hydraulic pressure is related with TGF-β1. Conclusion: We illustrate for the first time that hydraulic pressure can induce TEMT in a pressure magnitude- and duration-dependent manner, and that this TEMT is accompanied by TGF-β1 secretion.
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